Colonization and disruption of the epithelium is a major infection mechanism of mucosal pathogens. The epithelium counteracts infection by exfoliating damaged cells while maintaining the mucosal barrier function. The sexually transmitted bacterium Neisseria gonorrhoeae (Ng, also referred to in the art as GC) infect the female reproductive tract primarily from the endocervix, causing gonorrhea. However, the mechanism by which Ng overcomes the mucosal barrier remains elusive.
Ng, a Gram-negative bacterium, infects exclusively the mucosal surface of human genital tissues in men and women and causes gonorrhea, one of the most common sexually transmitted infections. In the female reproductive tract (FRT), the epithelium lining of endocervix has been suggested as a primary site for Ng to initiate infection that leads to pelvic inflammatory and disseminated diseases. Ng establishes infection by interacting with various receptors on epithelial cells, such as the binding of opacity-associate protein (Opa) to carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) or heparin sulfate proteoglycans (HSPG). These interactions alter signaling cascades in epithelial cells, such as phosphatidylinositol 3-kinase, phospholipase C, and Ca2+ flux. The signaling leads to actin reorganization, which drives microvillus elongation and the subsequent engulfment of Ng. However, how Ng manipulate columnar endocervical epithelial cells through their surface molecules for infection is unknown. A major obstacle against addressing this question has been a lack of infection models better mimicking aspects of human infection, which has in turn hampered the development of effective treatments and preventatives that can inhibit the establishment of Ng infection. Furthermore, The US Center for Disease Control and the World Health Organization have listed gonorrhea as an urgent public and women health issue. Gonorrhea is the second most common bacterial infection, affecting >800,000 people/year in the US and ˜80 million people worldwide. Gonorrhea can cause permanent disability and even death, and also increase the risk of HIV and other sexually transmitted diseases (STDs), which is estimated to cost the U.S. health care system ˜$17 billion/year. The most vulnerable population are women as STDs are considered a social taboo and most female gonorrhea are asymptomatic, which lead to treatment delay, further transmission, co-infection of other STDs, and severe complications, including chronic pelvic inflammation, life-threatening ectopic pregnancy, infertility, and disseminated infections. In addition to the lack of vaccines, there is also the issue of Ng developing resistance to antibiotics. US surveillance data suggest that it is only a matter of time before Ng becomes resistance to the only remaining effective antibiotics, cephalosporin. Thus, there is an urgent need for alternative preventives for gonorrhea not based on traditional antibiotics, and the development of such preventatives requires an improved research model for Ng infection. The present disclosure is pertinent to these needs.